Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics

Kudriavtsev, Aleksandr V.; Vakhrusheva, Anna; Novoseletsky, Valery; Bozdaganyan, Marine E.; Шайтан, К. В.; Kirpichnikov, Mikhaǐl P.; Sokolova, Olga S.

doi:10.3390/v14081603

Cited by 39 publications

(33 citation statements)

References 98 publications

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“…Importantly, the population-level impact of Omicron has been shaped by both its reduced per capita risk of mortality and severe disease, and by its increased transmissibility [ 878 ], particularly among those with pre-existing immunity, which resulted in higher total case counts. Most studies so far indicate that both BA.2 [ 872 , 879 , 880 ], BA.4 and BA.5 infected patients [ 674 , 881 , 882 , 883 ] show similar severity of COVID-19 compared to BA.1 infections.…”

Section: Viral Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

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Section: Viral Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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“…Out of six million people worldwide who have died from COVID-19, approximately one million died in the first half of 2022 [ 1 ]. A high viral transmission rate could lead to a quick virus evolution which may result in a strain with a higher transmissibility and/or virulence [ 2 ]. That said, novel mutant strains of the SARS-CoV-2, such as Omicron, can reinfect even those individuals who previously established immunity against the virus through disease or vaccination.…”

Section: Introductionmentioning

confidence: 99%

Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial

Kudriavtsev¹,

Vakhrusheva²,

Kryuchkov

et al. 2023

Vaccines

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COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies. The “Betuvax-CoV-2” vaccine, developed on the basis of a recombinant protein and an adjuvant, has already been tested in preclinical studies and has advanced to clinical evaluation. Open, double-blinded, placebo-controlled, randomized phase I/II clinical trial of the “Betuvax-CoV-2,” recombinant protein subunit vaccine based on the S-protein RBD fused with the Fc-fragment of IgG, was conducted to evaluate safety and immunogenicity in response to the vaccination. Methods: In the phase I/II clinical trial, 116 healthy adult men and women, ages 18–58, were enrolled: 20 in Stage I, and 96 in Stage II. In Stage I, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 1) or 20 µg (group 2) on day 30. In Stage II, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 3) or 20 µg (group 4) on day 30. In group 5, both injections were replaced with placebo. The primary outcome measures were safety (number of participants with adverse events throughout the study) and antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA and CMIA). Antigen-specific cell-mediated immunity and changes in neutralizing antibodies (detected with a SARS-CoV-2 neutralization assay) were measured as a secondary outcome. The trial is registered with ClinicalTrials.gov (Study Identifier: NCT05270954). Findings: Both vaccine formulations (20 µg + 5 µg and 20 µg + 20 µg) were safe and well tolerated. Most adverse events were mild, and no serious adverse events were detected. On day 51,anti-SARS-CoV-2 total and IgG antibody titers and anti-SARS-CoV-2 neutralizing antibodies were significantly higher in the vaccine groups (both formulations) than in the placebo. A more pronounced CD4+-mediated immune response was observed in the group of volunteers administered with the 20 + 20 μg vaccine formulation. Interpretations: RBD-Fc-based COVID-19 “Betuvax-CoV-2” vaccine in doses (20 + 5 µg and 20 + 20 µg) demonstrated an excellent safety profile and induced a strong humoral response. Further research on the protective effectiveness of the “Betuvax-CoV-2” vaccine for the prevention of COVID-19 is on its way.

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“…The Omicron strain of SARS-CoV-2 (B.1.1.529)—first identified in Botswana and South Africa in November 2021—has a large number of mutations in the surface protein. Omicron virus strains are responsible for a significant increase in incidence worldwide in late 2021 and January–February 2022 [ 48 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Filimonov

Yarovaya

Zaykovskaya

et al. 2022

Viruses

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In order to test the antiviral activity, a series of usnic acid derivatives were synthesized, including new, previously undescribed compounds. The activity of the derivatives against three strains of SARS-CoV-2 virus was studied. To understand the mechanism of antiviral action, the inhibitory activity of the main protease of SARS-CoV-2 virus was studied using the developed model as well as the antiviral activity against the pseudoviral system with glycoprotein S of SARS-CoV-2 virus on its surface. It was shown that usnic acid exhibits activity against three strains of SARS-CoV-2 virus: Wuhan, Delta, and Omicron. Compounds 10 and 13 also showed high activity against the three strains. The performed biological studies and molecular modeling allowed us to assume that the derivatives of usnic acid bind in the N-terminal domain of the surface glycoprotein S at the binding site of the hemoglobin decay metabolite.

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Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics

Cited by 39 publications

References 98 publications

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Safety and Immunogenicity of Betuvax-CoV-2, an RBD-Fc-Based SARS-CoV-2 Recombinant Vaccine: Preliminary Results of the First-in-Human, Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Trial

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

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